The present invention relates to a method for differentiating the source of occult gastrointestinal bleeding.
The common screening test for occult gastrointestinal bleeding is to test for fecal occult blood (FOB). An FOB test involves placing a sample of stool onto a testing surface and adding one or more reagents which react with the blood in the sample to produce a recognizable color.
Two current varieties of such tests are the HEMOCCULT device and the HEMAWIPE device. The HEMOCCULT test device requires that one use a small paddle to fish a feces sample out of the toilet and apply the sample to a piece of test paper mounted on a card. U.S. Pat. No. 3,996,006 to Pagano is exemplary of a HEMOCCULT test device.
The HEMAWIPE device utilizes a test pad adhered to a pliant impermeable base sheet and covered with a pliant volume control sheet having openings therein in alignment with the test pad. The patient can wipe with the HEMAWIPE device, remove the volume control cover sheet, fold the pliant base sheet over on itself to seal the test pad and sample and submit it for testing. A number of prior patents relate to the HEMAWIPE device including U.S. Pat. No. 4,808,379 entitled DEVICE FOR OBTAINING STOOL SAMPLES, issued Feb. 18, 1989; U.S. Pat. No. 4,804,518, entitled DEVICE FOR OCCULT BLOOD TESTING, issued Feb. 14., 1989; U.S. Pat. No. 4,559,949, entitled STOOL SAMPLING DEVICE, issued Dec. 24, 1985; U.S. Pat. No. 4,420,353, entitled METHOD OF MAKING A STOOL SAMPLING DEVICE, filed Dec. 13, 983; U.S. Pat. No. 4,367,750, entitled DEVICE FOR OBTAINING STOOL SAMPLES, issued Jan. 11, 1983; U.S. Pat. No. 4,273,741, entitled DEVICE FOR OBTAINING STOOL SAMPLES, issued Jun. 16, 1981; and U.S. Pat. No. 4,259,964 entitled DEVICE FOR OBTAINING STOOL SAMPLES, issued Apr. 7, 1981.
Virtually all FOB tests used today have the problem of nonspecificity. Their chemical reactions detect the peroxidase property of hemoglobin by causing the catalysis of peroxide into oxygen and water, and the subsequent oxidation of a colorless die into a colored form. Gum guaiac is the most commonly used color reagent, although a large number of other reagents have been used in the past.
The nonspecificity is due to two reasons. First, there are other peroxidase containing materials which the patient may eat, which, when excreted, will also cause a positive reaction. Second, blood from gastritis or dental bleeding can cause a positive reaction as well. While the hydrochloric acid present in the normal stomach converts the hemoglobin in the blood to hematin, hematin also has peroxidase activity material which can cause false-positives. Ideally, an FOB test would not only reliably detect blood but also give some indication as to the origin of the blood.
Since the FOB tests are more frequently used to screen patients for a hidden colonic malignancy, the consequences of missing any bleeding can be severe. Conversely, if there are a large number of false positive tests, the expense and possible complications of the additional follow-up tests involved are also considerable.
The ability to discriminate between the source of bleeding can play a pivotal role in the work-up and management of the patient with occult gastrointestinal bleeding. Detection of hematin in the stool will signify upper GI blood loss or the ingestion of peroxidases including blood in the diet. The clinician will be advised to repeat the test following dietary manipulation or proceed directly to upper endoscopy and/or radiographic study of the esophagus and stomach. Detection of hemoglobin in the stool, however, will focus clinical attention toward diseases of the distal GI tract including colonic carcinoma or polyposis, hemorrhoids or rectal fissures. The differential diagnosis will not be obscured by dietary sources or gastric stress ulcers, common causes of "false positive" results with HEMOCCULT and HEMAWIPE test systems.
There have been many attempts to make the FOB test more specific while preventing the undesired false positive results. Specific immunologic tests have been employed which are reactive only to human blood. The problem with these have been that they are much more complicated and expensive than the usual screening test, and the blood may be altered by partial digestion so that it is not detected by immunologic means. A recent technique called HEMAQUANT involves the extraction of a stool sample to obtain porphyrins, the breakdown products of blood. The advantage of this technique is that it is quantitative and relatively specific, but it too is expensive and much more cumbersome than the usual screening tests.
Therefore, there is a need to provide a FOB test which allows for the differential diagnosis of upper GI bleeding from lower GI bleeding which is inexpensive, easy to use, and provides adequate sensitivity, while preventing undesired false positive results.